This invention relates to a method of manufacturing structures and particularly polymeric tubular structures with complex and unique morphologies in the walls, and on the inner and outer surfaces of the structures.
Tubular structures have been prepared by a number of techniques, each of which has limitations for each application. For biomedical applications, a limitation is the abundant material required to prepare structures of limited size and shape, which can prove costly. For porous polymeric tubes, also known as hollow fiber membranes (HFMs), tubes with wall thicknesses on the order of hundreds of microns are prepared. There is no suitable method to prepare concentric, long HFMs, with thin walls, whether by dip-coating, spinning, or centrifugal casting, among others. As will be described in more detail, the invention comprises a process to prepare HFMs, or any hollow structure, with a broad range of wall and surface morphologies, dimensions and shapes. Such wall morphologies allow HFMs to be manufactured with considerably different transport properties while maintaining similar mechanical properties.
HFMs are commonly prepared by phase inversion through an annular die (or spinneret) where the solvent/non-solvent system controls many of the resulting properties, such as morphology of the wall structure. The dimensions are controlled by the spinneret, which must be finely tuned for concentricity. While the spinning technique has a proven record commercially, it requires abundant material and requires a certain amount of art to prepare reproducible HFMs.
Centrifugal casting is a process used to make a wide number of structures, both tubular and non-concentric (U.S. Pat. Nos. 5,266,325; 5,292,515). For manufacturing tubular shapes, a cylindrical mold is partially filled with a monomer, polymer melt, or monomer solution, and with air present inside the mold, coats the periphery of the mold under centrifugal action. The material spun to the outer portion of the mold is then held in place using temperature changes (cooling), polymerization or evaporation of the solvent. For this process, two phases are present inside the mold (air and liquid) before rotation; phase separation is not necessary for tubular formation. Wall morphologies are only attained by the addition of a porogen (salt, ethylene glycol etc.) that is leached out post-polymerization. Since air is required in the mold to form a tube (compared to a rod), attaining small diameter tubes with a small inner diameter on the micron scale cannot be achieved. Surface tension between the liquid and the gas inside the mold prevents miniaturization of the inner diameters for tens of centimeter length tubes.
For dip-coating, tubes are formed around a mandrel that is sequentially dipped in a polymer solution and non-solvent system, thereby coating the mandrel with the polymer via a phase inversion process. Alternately, the mandrel may be dipped in a polymer solution and the solvent left to evaporate. By these methods, the uniformity of the tube wall along the length of the tube is not well controlled.
It would therefore be very advantageous to manufacture tubes within a size regime, concentricity and with a multi-layering capability that is not presently achievable with the aforementioned methods.
The present invention provides a process of producing a product, comprising:
a) filling an interior of a mold with a solution so that substantially all air is displaced therefrom, the solution comprising at least two components which can be phase separated by a phase separation agent into at least two phases;
b) rotating said mold containing said solution at an effective rotational velocity in the presence of said phase separation agent to induce phase separation between said at least two components into at least two phases so that under rotation at least one of the phases deposits onto an inner surface of the mold; and
c) forming said product by stabilizing said at least one of the phases deposited onto the inner surface of the mold.
The present invention provides a product produced by the method, comprising:
a) filling an interior of a mold with a solution so that substantially all air is displaced therefrom, the solution comprising at least two components which can be phase separated by a phase separation agent into at least two phases;
b) rotating said mold containing said solution at an effective rotational velocity in the presence of said phase separation agent to induce phase separation between said at least two components into at least two phases so that under rotation at least one of the phases deposits onto an inner surface of the mold; and
c) forming said product by stabilizing said at least one of the phases deposited onto the inner surface of the mold.
The product formed by this process may be removed from the mold, or alternatively remain in the mold where the product and the mold are used for various applications. The product may be a polymeric material, in which case the solution includes either monomers or polymers or both.
The product may have a wall morphology that includes a porous structure, a gel structure or overlapping regions of porous/gel structure. The polymeric product may have a wall morphology that includes a predominantly gel morphology with porous channels running from a periphery to a lumenal side, resulting in spotting on an outer wall surface.
The polymeric product may be a multi-layered product produced by repeating steps a), b) and c), at least once to produce a multi-layered product.
The polymeric product may be used as a reservoir for the delivery of drugs, therapeutics, cells, cell products, genes, viral vectors, proteins, peptides, hormones, carbohydrates, growth factors.
The polymeric product may contain microspheres containing preselected constituents, and wherein the product includes said microspheres distributed either uniformly or in a gradient within the wall structure of the product.